Abstract

Background

Neuroinflammation contributes to the pathophysiology of acute CNS injury, including
traumatic brain injury (TBI). Although prostaglandin lipid mediators of inflammation
contribute to a variety of inflammatory responses, their importance in neuroinflammation
is not clear. There are conflicting reports as to the efficacy of inhibiting the enzymes
required for prostaglandin formation, cyclooxygenase (COX) -1 and COX-2, for improving
outcomes following TBI. The purpose of the current study was to determine the role
of the COX isoforms in contributing to pathological processes resulting from TBI by
utilizing mice deficient in COX-1 or COX-2.

Results

Following a mild controlled cortical impact injury, the amount of cortical tissue
loss, the level of microglial activation, and the capacity for functional recovery
was compared between COX-1-deficient mice or COX-2-deficient mice, and their matching
wild-type controls. The deficiency of COX-2 resulted in a minor (6%), although statistically
significant, increase in the sparing of cortical tissue following TBI. The deficiency
of COX-1 resulted in no detectable effect on cortical tissue loss following TBI. As
determined by 3[H]-PK11195 autoradiography, TBI produced a similar increase in microglial activation
in multiple brain regions of both COX-1 wild-type and COX-1-deficient mice. In COX-2
wild-type and COX-2-deficient mice, TBI increased 3[H]-PK11195 binding in all brain regions that were analyzed. Following injury, 3[H]-PK11195 binding in the dentate gyrus and CA1 region of the hippocampus was greater
in COX-2-deficient mice, as compared to COX-2 wild-type mice. Cognitive assessment
was performed in the wild-type, COX-1-deficient and COX-2-deficient mice following
4 days of recovery from TBI. There was no significant cognitive effect that resulted
from the deficiency of either COX-1 or COX-2, as determined by acquisition and spatial
memory retention testing in a Morris water maze.

Conclusion

These findings suggest that the deficiency of neither COX-1 nor COX-2 is sufficient
to alter cognitive outcomes following TBI in mice.